Climate change and the kidney

The worldwide increase in temperature has resulted in a marked increase in heat waves (heat extremes) that carries a markedly increased risk for morbidity and mortality. The kidney has a unique role not only in protecting the host from heat and dehydration but also is an important site of heat-associated disease. Here we review the potential impact of global warming and heat extremes on kidney diseases. High temperatures can result in increased core temperatures, dehydration, and blood hyperosmolality. Heatstroke (both clinical and subclinical whole-body hyperthermia) may have a major role in causing both acute kidney disease, leading to increased risk of acute kidney injury from rhabdomyolysis, or heat-induced inflammatory injury to the kidney. Recurrent heat and dehydration can result in chronic kidney disease (CKD) in animals and theoretically plays a role in epidemics of CKD developing in hot regions of the world where workers are exposed to extreme heat. Heat stress and dehydration also has a role in kidney stone formation, and poor hydration habits may increase the risk for recurrent urinary tract infections. The resultant social and economic consequences include disability and loss of productivity and employment. Given the rise in world temperatures, there is a major need to better understand how heat stress can induce kidney disease, how best to provide adequate hydration, and ways to reduce the negative effects of chronic heat exposure.Published versio

Prolonged acute kidney injury exacerbates lung inflammation at 7 days post‐acute kidney injury

Patients with acute kidney injury (AKI) have increased mortality; data suggest that the duration, not just severity, of AKI predicts increased mortality. Animal models suggest that AKI is a multisystem disease that deleteriously affects the lungs, heart, brain, intestine, and liver; notably, these effects have only been examined within 48 h, and longer term effects are unknown. In this study, we examined the longer term systemic effects of AKI, with a focus on lung injury. Mice were studied 7 days after an episode of ischemic AKI (22 min of renal pedicle clamping and then reperfusion) and numerous derangements were present including (1) lung inflammation; (2) increased serum proinflammatory cytokines; (3) liver injury; and (4) increased muscle catabolism. Since fluid overload may cause respiratory complications post-AKI and fluid management is a critical component of post-AKI care, we investigated various fluid administration strategies in the development of lung inflammation post-AKI. Four different fluid strategies were tested - 100, 500, 1000, or 2000 μL of saline administered subcutaneously daily for 7 days. Interestingly, at 7 days post-AKI, the 1000 and 2000 μL fluid groups had less severe AKI and less severe lung inflammation versus the 100 and 500 μL groups. In summary, our data demonstrate that appropriate fluid management after an episode of ischemic AKI led to both (1) faster recovery of kidney function and (2) significantly reduced lung inflammation, consistent with the notion that interventions to shorten AKI duration have the potential to reduce complications and improve patient outcomes

Hyperuricemia and chronic kidney disease: to treat or not to treat

Hyperuricemia is common in chronic kidney disease (CKD) and may be present in 50% of patients presenting for dialysis. Hyperuricemia can be secondary to impaired glomerular filtration rate (GFR) that occurs in CKD. However, hyperuricemia can also precede the development of kidney disease and predict incident CKD. Experimental studies of hyperuricemic models have found that both soluble and crystalline uric acid can cause significant kidney damage, characterized by ischemia, tubulointerstitial fibrosis, and inflammation. However, most Mendelian randomization studies failed to demonstrate a causal relationship between uric acid and CKD, and clinical trials have had variable results. Here we suggest potential explanations for the negative clinical and genetic findings, including the role of crystalline uric acid, intracellular uric acid, and xanthine oxidase activity in uric acid-mediated kidney injury. We propose future clinical trials as well as an algorithm for treatment of hyperuricemia in patients with CKD

Early peritoneal dialysis reduces lung inflammation in mice with ischemic acute kidney injury

Although dialysis has been used in the care of patients with acute kidney injury (AKI) for over 50 years, very little is known about the potential benefits of uremic control on systemic complications of AKI. Since the mortality of AKI requiring renal replacement therapy (RRT) is greater than half in the intensive care unit, a better understanding of the potential of RRT to improve outcomes is urgently needed. Therefore, we sought to develop a technically feasible and reproducible model of RRT in a mouse model of AKI. Models of low- and high-dose peritoneal dialysis (PD) were developed and their effect on AKI, systemic inflammation, and lung injury after ischemic AKI was examined. High-dose PD had no effect on AKI, but effectively cleared serum IL-6, and dramatically reduced lung inflammation, while low-dose PD had no effect on any of these three outcomes. Both models of RRT using PD in AKI in mice reliably lowered urea in a dose-dependent fashion. Thus, use of these models of PD in mice with AKI has great potential to unravel the mechanisms by which RRT may improve the systemic complications that have led to increased mortality in AKI. In light of recent data demonstrating reduced serum IL-6 and improved outcomes with prophylactic PD in children, we believe that our results are highly clinically relevant

Reporte de Mercados Financieros - Primer trimestre de 2023

El Banco de la República (Banrep) genera información para la toma de decisiones, la rendición de cuentas y la difusión al público. En particular, el \textit{Reporte de Mercados Financieros} está enmarcado dentro del principio de difusión al público y contribuye a cumplir con el servicio que presta el Banco de ofrecer información e investigación económica de calidad. En línea con lo anterior, este reporte busca proveer al público un análisis general del comportamiento y las tendencias de los mercados financieros nacionales e internacionales. Adicionalmente, señala los principales factores que permiten explicar el comportamiento de dichos mercados y sus interacciones, sí como una descripción de los principales cambios en política monetaria y decisiones de los bancos centrales a nivel mundial. El entorno económico global en el que se desenvuelven los mercados que este reporte estudia, continúa inmerso en un escenario de bajas perspectivas de crecimiento, una inflación que sigue sorprendiendo por su alta persistencia, tensiones geopolíticas y la presencia de factores de riesgo en el frente financiero que pueden materializarse ante un escenario macroeconómico más complejo. Por su parte, los agentes del mercado han balanceado diferentes fuentes de información para discernir acerca de la posible senda de la política monetaria global, dados sus efectos en los distintos mercados. Sin embargo, al final del primer trimestre de 2023 primó la expectativa de una postura menos contractiva por parte de la Fed, teniendo en cuenta que aunque las autoridades han manifestado su valoración sobre la resiliencia del sector bancario tras la quiebra de algunos bancos regionales, se percibe una alta reactividad de los inversionistas ante las noticias sobre el desempeño de los sectores económicos, la inflación, el mercado laboral y la dinámica del crédito y, por tanto, en las condiciones financieras en EE.UU (Ver Entorno Internacional). Con respecto a la evolución de las variables macroeconómicas y las expectativas de la evolución de la política monetaria futura en el contexto local, los agentes del mercado descuentan para 2023 una senda de inflación decreciente y una desaceleración en la dinámica económica consistente con perspectivas de una postura de política monetaria contractiva por parte del Banrep. En este entorno, el mercado descuenta para el segundo trimestre del año el fin del ciclo de incrementos de la tasa de interés de referencia por parte del Banrep así como el inicio de reducciones en la tasa de interés hacia el segundo semestre del año (Ver política monetaria y mercado monetario local). Con respecto al mercado de deuda pública local, este presentó un comportamiento favorable, superior a los pares de la región, que contrasta con su comportamiento durante 2022, en línea con la reducción en las perspectivas de tasa de política monetaria de la Fed y una mayor liquidez de este mercado. En todo caso, las tasas en este mercado sugieren un costo de financiamiento relativamente elevado (ver Mercado de deuda pública interna y externa – Gráfico 1). El mercado monetario exhibió amplios niveles de liquidez que se corrigieron durante el periodo. Al mismo tiempo, persiste una alta percepción de riesgo país, que coincide con la permanencia de fuentes de vulnerabilidad externa y fiscal, así como con la incertidumbre sobre el desenlace de la agenda de reformas del gobierno (Ver Percepción de riesgo a nivel local). Como consecuencia, los inversionistas extranjeros realizaron ventas de títulos de deuda pública en el trimestre, aunque se observó un comportamiento volátil y las ventas fueron realizadas por algunos agentes puntuales y estuvieron concentradas en algunas referencias específicas. Por su parte, para la deuda privada, se identifica un fuerte dinamismo del mercado de CDTs en el periodo reciente, mientras que las colocaciones en otros títulos de deuda privada siguen perdiendo dinamismo (Ver Mercado de deuda privada). En este reporte se estudia los factores que pudieron guiar el fuerte aumento del diferencial entre los CDTs y los TES en el periodo reciente. Se encuentran indicios de una posible relación entre el spread con factores tales como la tasa de política monetaria y sus expectativas, unas mayores expectativas de inflación, un alto crecimiento de la cartera acompañado de la entrada en vigor del CFEN, una alta concentración en el mercado de tenedores de CDT y una mayor percepción de riesgo (Ver Recuadro 1. Análisis del spread entre las tasas de los CDT y TES). En cuanto al mercado cambiario, el peso colombiano se apreció y volvió a niveles no vistos en cerca de seis meses, en línea con correcciones en la fortaleza del dólar a nivel internacional. No obstante, sus niveles se mantienen aún desviados de las monedas de los países pares de la región (Ver Mercado Cambiario – Gráfico 1). Finalmente, el mercado accionario local, continúa exhibiendo un desempeño débil en comparación con los pares de la región, en un entorno de baja liquidez. Las acciones del sector bancario, que tienen un peso importante sobre índice local presentaron caídas importantes, en línea con las referencias globales, ante los eventos adversos en algunas entidades financieras de EE. UU. y Suiza (Ver Mercado accionario – Gráfico 1)

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217

Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

publishersversionPeer reviewe

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Dementia in Latin America : paving the way towards a regional action plan

Regional challenges faced by Latin American and Caribbean countries (LACs) to fight dementia, such as heterogeneity, diversity, political instabilities, and socioeconomic disparities, can be addressed more effectively grounded in a collaborative setting based on the open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking and translational research) and align them to current global strategies to translate regional knowledge into actions with transformative power. Then, by characterizing genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions and mapping these to the above challenges, we provide the basic mosaics of knowledge that will pave the way towards a KtAF. We describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF